Boron neutron capture therapy (BNCT) is being developed as a treatment for cancer, including malignant melanoma. P-boronophenylalanine (BPA) was initially proposed as a boron (B) delivery drug for BNCT of malignant melanoma because it was postulated that this B-containing amino acid, by mimicking a melanin precursor, would selectively accumulate in melanoma cells. BPA does seem to selectively accumulate in melanocytes, apparently as a result of uptake by an amino acid transport system. For successful BNCT, tumor B concentrations of at least 20 ppm are thought to be necessary, but higher tumor B levels are desirable. Calculations indicate that for a given neutron exposure, each doubling of the tumor B concentration should increase tumor cell kill by a factor of about 10,000. Thus, even modest increases in the amount of B in tumor cells can dramatically improve the effectiveness of BNCT as a cancer treatment.
If amino acid transport systems accumulate BPA, then high extracellular concentrations of BPA should increase the amount of BPA entering melanocytes. I.V. infusion of BPA is the simplest route for delivering BPA to the tumor cells but is not widely used because at physiological pH (7.4), BPA exhibits poor water solubility (&lt;4 ppm). One option for increasing BPA solubility is the use of organic complexes. Boric acid is known to complex with monosaccharides. Monosaccharides also increase BPA's aqueous solubility. However, BPA exists in different forms at different pH values and complexing of BPA with monosaccharides is a pH dependent process. I.V. administration of BPA-monosaccharide complexes created by pH manipulation increases the delivery of B to tumor tissue.